Profile: Pioneering new treatment for neurological disorders

By Kimberley Wang, Manager, Media and Publications, Communications and Outreach

As a clinician-scientist, LKCMedicine Associate Professor Yasunori Saheki is known for his work on lipid homeostasis in neuronal function and neurodegeneration. He has done groundbreaking work at the School that lays the foundation for developing new treatments to counteract neurological disorders.  

Recently promoted to Associate Professor in September, he continues to work closely with his lab members to deepen understanding of the mechanisms behind lipid transport in cells in order to develop novel therapies for neurodegenerative disorders such as Alzheimer’s disease and Parkinson’s disease.

Developing novel therapies for neurodegenerative disorders

Employing an interdisciplinary approach that combines mammalian cell biology, biochemistry and Caenorhabditis elegans (a nematode used as one of the most popular model animals for biomedical research) genetics, A/Prof Saheki seeks to identify new therapeutic targets by studying general principles of cellular lipid homeostasis and how these pathways are critical for neuronal and brain function. 

He explained, “We are investigating how the levels of various lipids, including cholesterol, are maintained across different cellular membranes. Lipids are unevenly distributed in cells. In particular, cholesterol is highly enriched in the plasma membrane – the membrane wrapping around the cell – where it contributes to membrane integrity and cell signalling.

“Abnormal distribution of cholesterol is associated with various diseases in humans, including heart attacks and dementia. However, it remains unclear how cells maintain such uneven distribution of cholesterol. To tackle this challenge, we have been characterising the functions of lipid transport proteins that are responsible for distribution of cholesterol and other lipids in cells.”

In the future, A/Prof Saheki and his team aim to build on their new discoveries on intracellular lipid transport to develop a drug that can modulate or fix lipid distribution in cells.

He emphasised the critical need for research in this area in light of the increasing burden of neurodegenerative disorders, including Alzheimer’s disease and Parkinson’s disease, especially since there is currently no cure for neurodegeneration. 

“It is an urgent need of our society to come up with a novel therapeutic approach to counteract neurodegeneration. Abnormal distribution of lipids in cells has been associated with neurodegeneration. However, how exactly healthy cells transport lipids to maintain their distribution remains unclear,” he said.

“By understanding the fundamental mechanisms behind lipid transport in cells, we could potentially come up with a novel therapeutic approach to treat patients who are suffering from neurodegenerative disorders.” 

A/Prof Saheki’s research impact has also gained international visibility. In 2020, he was recognised by the European Molecular Biology Organization (EMBO) and selected as an EMBO Global Investigator along with eight other scientists from around the world. 

Drawing on his experience in the field, he has this advice for young researchers: “Research is like a marathon. Maintain good work-life balance to keep yourself excited and motivated with your research. Stay focused on your research goals and keep yourself up to date with various literatures in the field.” 

At the same time, A/Prof Saheki will carry on teaching LKCMedicine MBBS and PhD students the foundation of medicine and molecular neuroscience. He said, “I enjoy stimulating the curiosity of our students and helping them to be passionate about the subjects I teach. It is a joy to see our students leave my class with excitement and happiness. One day they will become doctors and scientists, and I am here hoping to help them to be lifelong learners.” 

Curiosity paved the way to a thriving research career

Describing himself as “positive, curious, and meticulous”, A/Prof Saheki developed an inquisitive nature from a young age. 

His grandfather, Tsuneo Saheki, was an internationally renowned astronomer who dedicated five decades to observing Mars and noted flashes of light known as flares on the planet. To honour his contributions to astronomy, the International Astronomical Union named a crater on Mars and an asteroid after Saheki.  

As a child, A/Prof Saheki was fascinated by picture books of animals in his grandfather’s library whenever he went to visit.

“In his study, there was a gigantic shelf displaying different types of books, ranging from textbooks of outer space to picture books of reptiles. I remember I was always attracted to picture books of living creatures, such as insects and reptiles,” he recalled. 

Growing up in a suburb near Kobe, he enjoyed running around a paddy field and capturing various insects, such as grasshoppers and mantis, and small reptiles like frogs and lizards. With a strong scientific curiosity, he often brought them home to observe how they would move and eat.  

During the summer, he and his sister conducted their own research, including raising silkworms to find out how they eventually grow to be moths and studying how long it takes for eggs to float in salty water. They would also make posters to present their findings. 

Other childhood activities also stirred up his interest in research. “I was often taken by my parents to visit science museums on weekends, being exposed to a wide variety of topics from astronomy, chemistry to physics. These experiences taught me the excitement of research regardless of the topic,” he said.

Whenever he has time away from work, A/Prof Saheki spends most of it with his wife and two young children. “I enjoy playing with them to learn from their rapid growth and development,” he shared.